Sympathetic and parasympathetic interaction in vascular and secretory control of the nasal mucosa in anaesthetized dogs.
1. In dogs anaesthetized with pentobarbitone, electrical stimulation of the parasympathetic nerve fibres to the nasal mucosa evoked frequency dependent increases in both nasal arterial blood flow and nasal secretion. Blood flow was measured using a transonic flow probe placed around the artery. 2. Sympathetic nerve stimulation for 3 min at 10 Hz evoked significant and prolonged (> 30 min) attenuation of the vasodilator and secretory responses to subsequent parasympathetic stimulation. 3. Intravenous and intranasal administration of the neuropeptide Y (NPY) analogue N-acetyl [Leu28,Leu31] NPY 24-36, a selective NPY Y2 receptor agonist (20 nmol kg-1), significantly attenuated both vasodilator and secretory effects of subsequent parasympathetic nerve stimulation. When given intravenously, the inhibitory effect of this Y2 receptor agonist on vascular and secretory effects of parasympathetic nerve stimulation was rapid in onset (5 min) and lasted for more than 60 min. The modulatory effect of the Y2 receptor agonist was also seen with intranasal administration, but was slower in onset (15 min), and lasted less than 45 min. The effects of the intranasal pretreatment with the Y2 receptor agonist were significantly prolonged in the presence of the endopeptidase inhibitor phosphoramidon (10 nM). 4. Atropine pretreatment did not significantly reduce the change in vascular conductance evoked by parasympathetic nerve stimulation. Subsequent pretreatment with the NPY Y2 receptor agonist N-acetyl [Leu28,Leu31] NPY 24-36 reduced the stimulation induced increase in conductance by 30%. Nasal secretion was reduced by 70% following pretreatment with atropine and a further 30% by pretreatment with the NPY Y2 receptor agonist. Dose dependent vasodilator and secretory effects of local intra-arterial infusion of acetylcholine and vasoactive intestinal peptide were not modified by the NPY Y2 agonist. 5. Total protein and albumin concentration were measured in nasal lavage fluid collected after nerve stimulation. Atropine pretreatment increased the percentage of the total protein that was albumin in nasal lavage fluid. Neither sympathetic nerve stimulation nor Y2 receptor agonist pretreatment further modified the albumin exudation (a marker of vascular permeability) in nasal fluid lavage collected after parasympathetic nerve stimulation. 6. We propose that sympathetic nerve stimulation releases NPY, which acts on Y2 receptors, probably located on parasympathetic nerve endings, to attenuate both vasodilatation and nasal secretion evoked by subsequent parasympathetic nerve stimulation. This effect is also observed after pretreatment with the Y2-selective NPY analogue N-acetyl [Leu28,Leu31] NPY 24-36.
Revington
M
M
Prince of Wales Medical Research Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
Lacroix
J S
JS
Potter
E K
EK
D000281:Administration, Intranasal; D000418:Albumins / Q000378:metabolism; D000758:Anesthesia; D000818:Animals; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D009297:Nasal Mucosa / Q000098:blood supply* / Q000294:innervation / Q000378:metabolism*; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000819:agonists; D013564:Sympathetic Nervous System / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000418:Albumins; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C084653:neuropeptide Y (24-36), Ac-(Leu(28,31))-; C095889:neuropeptide Y2 receptor